α-Lipoic Acid Inhibits Expression of IL-8 by Suppressing Activation of MAPK, Jak/Stat, and NF-κB in H. pylori-Infected Gastric Epithelial AGS Cells.
α-Lipoic Acid Inhibits Expression of IL-8 by Suppressing Activation of MAPK, Jak/Stat, and NF-κB in H. pylori-Infected Gastric Epithelial AGS Cells.
复制标题
DOI：
10.3349/ymj.2016.57.1.260
复制
发表时间：
2016-01
影响因子：
2.4
通讯作者：
Kim H
中科院分区：
文献类型：
--
作者：
Choi JH;Cho SO;Kim H
与活性氧 (ROS) 相关的上皮细胞因子反应在幽门螺杆菌 (H. pylori) 诱导的炎症中非常重要。 H. pylori 诱导 ROS 的产生，ROS 可能参与丝裂原激活蛋白激酶 (MAPK)、Janus 激酶/信号转导器和转录激活子 (Jak/Stat) 以及氧化剂敏感转录因子、活化 B 细胞核因子 kappa 轻链增强子 (NF-κB) 的激活，从而参与白细胞介素 8 的表达 (IL-8) 存在于胃上皮细胞中。 α-硫辛酸是一种天然存在的硫醇化合物，是一种潜在的抗氧化剂。它在治疗包括糖尿病在内的氧化相关疾病方面显示出有益的作用。本研究旨在探讨α-硫辛酸是否通过抑制幽门螺杆菌感染的胃上皮细胞中MAPK、Jak/Stat和NF-κB的激活来抑制炎症细胞因子IL-8的表达。胃上皮AGS细胞用或不用α-硫辛酸预处理2小时，并以300:1的比例感染韩国分离株（HP99）中的幽门螺杆菌。通过RT-PCR分析来分析IL-8 mRNA表达。通过酶联免疫吸附测定法测定培养基中的IL-8水平。通过电泳迁移率变动测定法测定 NF-κB-DNA 结合活性。通过蛋白质印迹分析评估 MAPK 和 Jak/Stat 的磷酸特异性和总形式。使用二氯荧光素荧光测定ROS水平。结果，幽门螺杆菌诱导 AGS 中 ROS 水平、mRNA 和 IL-8 蛋白水平增加，以及 MAPK [细胞外信号调节激酶 1/2 (ERK1/2)、c-Jun NH2 末端激酶 1/2 (JNK1/2)、p38]、Jak/Stat (Jak1/2、Stat3) 和 NF-κB 的激活 细胞，其被α-硫辛酸抑制。总之，α-硫辛酸可能有益于预防和/或治疗幽门螺杆菌感染相关的胃炎症。
The epithelial cytokine response, associated with reactive oxygen species (ROS), is important in Helicobacter pylori (H. pylori)-induced inflammation. H. pylori induces the production of ROS, which may be involved in the activation of mitogen-activated protein kinases (MAPK), janus kinase/signal transducers and activators of transcription (Jak/Stat), and oxidant-sensitive transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and thus, expression of interleukin-8 (IL-8) in gastric epithelial cells. α-lipoic acid, a naturally occurring thiol compound, is a potential antioxidant. It shows beneficial effects in treatment of oxidant-associated diseases including diabetes. The present study is purposed to investigate whether α-lipoic acid inhibits expression of inflammatory cytokine IL-8 by suppressing activation of MAPK, Jak/Stat, and NF-κB in H. pylori-infected gastric epithelial cells. Gastric epithelial AGS cells were pretreated with or without α-lipoic acid for 2 h and infected with H. pylori in a Korean isolate (HP99) at a ratio of 300:1. IL-8 mRNA expression was analyzed by RT-PCR analysis. IL-8 levels in the medium were determined by enzyme-linked immunosorbent assay. NF-κB-DNA binding activity was determined by electrophoretic mobility shift assay. Phospho-specific and total forms of MAPK and Jak/Stat were assessed by Western blot analysis. ROS levels were determined using dichlorofluorescein fluorescence. As a result, H. pylori induced increases in ROS levels, mRNA, and protein levels of IL-8, as well as the activation of MAPK [extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase 1/2 (JNK1/2), p38], Jak/Stat (Jak1/2, Stat3), and NF-κB in AGS cells, which was inhibited by α-lipoic acid. In conclusion, α-lipoic acid may be beneficial for prevention and/or treatment of H. pylori infection-associated gastric inflammation.